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Contribution of CXCR4(+)/PDGFRbeta(+) progenitor cells in hypoxic alveolar arterioles muscularization: role of myocardin.

AbstractAIMS:
Bone marrow (BM) progenitor cells may contribute to vascular remodelling. The present study aimed to investigate the contribution of BM-derived CXCR4(+) (a CXC chemokine receptor) and PDGFRbeta(+) (platelet-derived growth factor receptor beta) progenitor cells in hypoxia-induced muscularization of alveolar arterioles.
METHODS AND RESULTS:
Accumulation of GFP(+) (green fluorescent protein) cells was markedly increased in the pulmonary vasculature by the hypoxic (10% O(2,) 4 weeks) chimeric mice with transgenic GFP-tagged BM. After injection of BM-derived CXCR4(+)/PDGFRbeta(+) progenitor cells into C57BL/6J mice, followed by 6-week hypoxia, the cells were found to home to the alveolar arterioles and readily differentiated into smooth muscle cells (SMCs). Under the same hypoxic conditions, mice infused with myocardin lentiviral RNAi vector-transduced progenitor cells displayed lower myocardin expression in the muscularized alveolar arterioles, correlating with decreased pulmonary artery pressure and arteriole muscularization. In vitro experiments further confirmed that the differentiation of the progenitor cells into SMCs occurred under hypoxia (1% O(2)), and SMC differentiation could be suppressed when myocardin RNAi was administered.
CONCLUSION:
Theses results suggest that myocardin may contribute to the differentiation of CXCR4(+)/PDGFRbeta(+) progenitor cells into SMCs induced by hypoxia, which leads to the muscularization of alveolar arterioles.
AuthorsWei Jie, Xiaoyan Wang, Lei Huang, Junli Guo, Dong Kuang, Pengcheng Zhu, Mei Li, Xia Zhao, Yaqi Duan, Guoping Wang, Qilin Ao
JournalCardiovascular research (Cardiovasc Res) Vol. 87 Issue 4 Pg. 740-50 (Sep 01 2010) ISSN: 1755-3245 [Electronic] England
PMID20484220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CXCR4 protein, mouse
  • Nuclear Proteins
  • Receptors, CXCR4
  • Trans-Activators
  • myocardin
  • Green Fluorescent Proteins
  • Receptor, Platelet-Derived Growth Factor beta
Topics
  • Animals
  • Arterioles (immunology, metabolism)
  • Blood Pressure
  • Bone Marrow Cells (immunology, metabolism)
  • Bone Marrow Transplantation
  • Cell Differentiation
  • Cell Movement
  • Disease Models, Animal
  • Green Fluorescent Proteins (biosynthesis, genetics)
  • Hypoxia (immunology, metabolism, physiopathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle, Smooth, Vascular (immunology, metabolism)
  • NIH 3T3 Cells
  • Nuclear Proteins (genetics, metabolism)
  • Pulmonary Alveoli (blood supply)
  • RNA Interference
  • Receptor, Platelet-Derived Growth Factor beta (metabolism)
  • Receptors, CXCR4 (metabolism)
  • Stem Cell Transplantation
  • Stem Cells (immunology, metabolism)
  • Time Factors
  • Trans-Activators (genetics, metabolism)
  • Transplantation Chimera

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